Over the past two decades, the field of tissue engineering has focused on the repair and reconstruction of tissue utilizing scaffolds, both as a means to culture cells in vitro for subsequent implantation in vivo and as an acellular implant to encourage tissue ingrowth and incorporation. Scaffolds seeded and cultured with cells are utilized to deliver and/or direct cells to desired sites in the body, to define a potential space for engineered tissue, and to guide the process of tissue development. In the case of cell culture, cell transplantation, on or from scaffolds, has been explored for the regeneration of skin, nerve, liver, pancreas, cartilage, adipose and bone tissue, using various biological and synthetic materials.
Acellular scaffolds have also been developed for promoting the attachment and migration of cells from the surrounding living tissue to the surface and interior of the scaffold. In these cases, bioabsorbable materials are useful in order to provide a substrate for incipient tissue growth and subsequent degradation and elimination from the area leaving behind newly regenerated tissue. Examples of such materials include poly(lactic acid) (PLA), poly(caprolactone) (PCL), poly(glycolic acid) (PGA), poly(dioxanone) (PDO), poly(trimethylene carbonate) (TMC), and their copolymers and blends.
Scaffolds, whether acellular or seeded, have certain requirements with regards to the penetration of the scaffold by cells and the nutrient flow to cells. Scaffolds with pores of diameters up to 500 microns provide sufficient open space for the formation of functional tissue, but lack the means necessary to provide sufficient infiltration of cells, diffusion of nutrients and oxygen to the cells, removal of metabolic waste away from the cells, and to guide the cells and fluids.
Several attempts to provide scaffolds with architectures to improve the diffusion of nutrients through the scaffold have been made in the recent past. These include bimodal porous structures that enhance the available surface area and internal volume of the scaffold. These structures were created using leachable particles incorporated into either a polymer or a polymer solution. In the case of the polymer solution, freeze drying was used to create a polymer foam embedded with leachable particles. The foam was then subjected to a subsequent step in which the particles were leached out of the system to create a second set of pores.
Alternatively, biocompatible porous polymer membranes were prepared by dispersing salt particles in a biocompatible polymer solution. The solvent was evaporated and the salt particles were leached out of the membrane by immersing the membrane in a solvent for the salt particles. A three-dimensional porous structure was then manufactured by laminating the membranes together to form the desired shape.
Others have circumvented the use of leachable particles to form porous membranes of various pore diameters by casting a layer of polymer solution on a substrate and submerging the layer/substrate in a non-solvent for the polymer. This created a porous a polymer structure. The cast layers were laminated to achieve gradients in porosity in the three-dimensional structure.
Still others have used a rigid-coil/flexible-coil block copolymer mixed with a solvent that selectively solubilized one of the blocks. The other block of the copolymer was permitted to self-assemble into organized mesostructures. The solvent was then evaporated, leaving the structure mesoporous.
The field of tissue engineering to repair and reconstruct tissue has utilized scaffolds to encourage tissue ingrowth and incorporation, scaffolds in the form of porous polymer foams. The morphology of foams has progressed from random to controlled formation, but the controlled morphology has resulted either in a monomodal, isotropic distribution of pores through spinodal decomposition of polymer solvent mixtures or in the production of uniaxial channels in the foam. There remains a need for biodegradable porous polymer scaffolds for tissue engineering that have an architecture providing for the effective and thorough distribution of fluids and nutrients necessary for tissue growth. In addition, it would be advantageous to be able to produce this scaffold by way of a method that does not require any manipulation of the material post-processing.